Immunotherapy with subcutaneous low-dose interleukin-2 and the pineal indole melatonin as a new effective therapy in advanced cancers of the digestive tract

• Published in: British journal of cancer 1993-06, Vol.67 (6), p.1404-1407
• Main Authors: LISSONI, P, BARNI, S, CHARACIEJUS, D, KOTHARI, L, CONTI, A, MAESTRONI, G. J. M, TANCINI, G, ARDIZZOIA, A, ROVELLI, F, CAZZANIGA, M, BRIVIO, F, PIPERNO, A, ALDEGHI, R, FOSSATI, D
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Digestive System Neoplasms - therapy; Dose-Response Relationship, Drug; Drug Synergism; Eosinophils - drug effects; Female; Humans; Immunotherapy; Interleukin-2 - administration & dosage; Interleukin-2 - adverse effects; Lymphocytes - drug effects; Male; Medical sciences; Melatonin - administration & dosage; Melatonin - adverse effects; Middle Aged; Pharmacology. Drug treatments
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.1993.260

The advanced tumours of the digestive tract are generally less responsive to conventional chemotherapies. Moreover, preliminary results with IL-2 immunotherapy also seem to show a low efficacy. On the basis of our previous studies suggesting s synergistic action between IL-2 and some neurohormones, such as the pineal indole MLT, a clinical trial was performed to investigate the clinical efficacy and tolerability of an immunotherapy with IL-2 plus MLT in patients with advanced neoplasms of the digestive tract. The study included 35 patients (colorectal cancer: 14; gastric cancer: 8; hepatocarcinoma: 6; pancreas adenocarcinoma: 7). Distant organ metastases were present in 31/35 patients. MLT was given orally at a daily dose of 50 mg at 8.00 p.m., starting 7 days before IL-2, which was given subcutaneously at a dose of 3 million IU/day at 8.00 p.m. for 6 days/week for 4 weeks, corresponding to one cycle of immunotherapy. In nonprogressed patients, a second cycle was given after a 21-day rest period. A complete response was achieved in two patients (gastric cancer: 1; hepatocarcinoma: 1). Six other patients obtained a partial response: (gastric cancer: 2; hepatocarcinoma: 2; colon cancer: 1; pancreas cancer: 1). Therefore, the overall response rate was 8/35 (23%). Stable disease was obtained in 11/35 (31%) patients, whereas the remaining 16 patients (46%) progressed. The response rate was significantly higher in untreated patients than in those previously treated with chemotherapy. Toxicity was low in all patients, who received the treatment as a home therapy. This study shows that the immunotherapy with low-dose IL-2 plus the pineal hormone MLT is a new well tolerated and effective therapy of advanced tumours of the digestive tract, mainly in gastric cancer and hepatocarcinoma.